Previous studies using magnetic resonance spectroscopy have related abnormalities in hippocampal metabolism to depression. Current evidence is consistent with the conclusion that the hippocampal formation plays an important role in the presentation of depressive symptoms. Eighteen adult patients with major depressive disorder, aged 20 to 60 years, underwent magnetic resonance spectroscopy of the hippocampus during a period of depressive symptomatology and after 7-11 weeks of antidepressant medication with at least 50% reduction in the Montgomery-Åsberg Depression Rating Scale ()MADRS score. During therapy, we found a significantly decreased Lac/Cr ratio in the left hippocampus. The Ins/Cr ratio showed a significant negative correlation with the severity of depression as assessed by the MADRS at baseline. Moreover, we found a negative association of NAA/Cho with age and a positive association of Cho/Cr with age, both on the left and right sides at baseline. In light of our findings and previous studies results we hypothesize that mitochondrial dysfunction leading to predominantly anaerobic glycolysis in connection with the intracellular signaling pathways disturbances and decreased astrocytic function/number might subsequently lead to decreased brain neuroplasticity in depression. These mechanisms could be positively influenced by antidepressant treatment with selective serotonin or norepineprine reuptake inhibitors, with potential effects on untimely neuronal aging in depression.

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